Why study African trypanosomes?

We’ve always needed to be able to justify our chosen area of research, and this is particularly the case in current times when funding is so hard to come by. This question is also pertinent given the recent successes achieved in controlling Human African Trypanosomiasis (HAT) by numerous NGOs, the WHO, and many African public health professionals and institutions. Their efforts have led to a collapse in recorded cases, a trend that has resulted in less than 7,000 incidents of HAT being reported in 2011 (Simmarro et al, 2012). These successes inspired the WHO in Africa to propose that HAT should be eliminated as a public health problem by 2015 (WHO Africa) – though this should not be confused with full elimination or eradication of HAT, and even if achieved, surveillance measures will need to be maintained.

So why do so many of us still work on Trypanosoma brucei, the African trypanosome?

One simple answer is that people are still dying from HAT. The available drugs have been in use for many years (almost 100 in the case of suramin), they are toxic with a whole collection of extremely unpleasant side effects, they are complex to adminsister (requiring prolonged use, and hospitalisation of the patient), and the incidence of treatment failures and resistance is on the rise (Barrett et al, 2011). Without treatment HAT is fatal – in weeks to months in the case of East African HAT, while West African HAT can take  months to years to cause death (Brun et al, 2010). Although, it should be noted that a recent report has shown that some individuals can become aparasitaemic, asymptomatic and present a declining serological response, even in the absence of treatment (Jamonneau et al, 2012). How widespread this apparent ‘trypanotolerance’ is within the HAT at-risk population is unknown, as is the potential for ‘reactivation’ in these individuals.

The reported case numbers are a gross underestimate of the real situation. The WHO estimates that in 2011 there were nearer to 30,000 cases (WHO Factsheet 259). This is due to a number of factors, including poor accessibility to some endemic areas, stigma associated with the disease preventing sufferers from seeking help, and misdiagnosis (symptoms are non-specific). In fact the true situation may be even worse as, due to its speed of progress, many East African HAT sufferers are simply missed (Odiit et al, 2005). Though given all this, case numbers are the lowest they’ve been for many years, and elimination, may be an achievable goal (Welburn & Maudlin, 2012), though not necessarily within the ambitious time frame set by WHO Africa.

Unfortunately, we’ve been here before. Extensive control efforts, focusing on reducing the number of tsetse flies (the vector) and reservoir animals in endemic areas, led to a massive reduction in the number of HAT cases throughout the 1960s. At this time a combination of civil conflict and complacency led to the failure of these early control efforts and HAT resurged, with the resultant epidemic reaching its peak in the mid 1990s. Hence, it is now, when case numbers are at a 50 year low, that control efforts need to be maintained, if not redoubled, for HAT elimination to be achieved; especially given the issues with the available drugs and the potential for significant civil conflict in the region, which can lead to population displacement into endemic areas (Berrang Ford, 2007; Ruiz-Postigo et al, 2012).

It’s not only humans who suffer from the ravages of this devastating disease. African trypanosomes also parasitise other mammals, including livestock and wild ungulates (antelope, wildebeest, etc), and many of these animals can act as resevoirs of human infection – the existence of so many resevoirs of HAT is just one significant obstacle among many that make control of this disease, let alone elimination, a huge challenge. So, even though HAT as a public health problem is currently declining, these parasites are still having a massive impact on livelihoods and health in Africa through their detrimental effect on livestock farming. In fact, T. brucei and the related trypansomes, T. conglense and T.vivax, have had a restrictive effect on the development of livestock farming in Africa over millennia, and this is still the case today in endemic areas. Just as for HAT, there is only a limited set of drugs available and parasite resistance to these is a serious problem (Geerts et al, 2001).

Surely, the above is reason enough to continue working on T. brucei?

The African trypanosome isn’t the only trypanosomatid to cause devastating disease. The American trypanosome, T. cruzi, causes Chagas’ disease in Central and South America, and Leishmania, a group of related trypanosomatids, causes a collection of diseases throughout the tropics and sub-tropics. Genetically, these three groups of parasites are very similar, though there are significant differences, not least of which is that T. cruzi and Leishmania are intracelllular parasites, while T. brucei is extracellular. Although T. cruzi and Leishmania are extensively studied in labs around the world, neither is as genetically tractable as T. brucei. Therefore, initial experiments in T. brucei can help to set the direction and priorities for later work in these other parasites, potentially saving a huge amount of time in the process.

Finally, the trypanosomatids (trypanosomes and Leishmania) are intrinsically interesting for the many unusual aspects of their biology, due in part to their position at the root of the eukaryotic tree of life. They provide a highly divergent comparator, giving a different perspective (for example see, Dubois et al, 2012, and Field et al, 2012) from the evolutionarily closely related group of widely studied ‘model’ organisms, such as Drosophila, C. elegans, the yeasts, Xenopus and mammals.

For all of this though, the most important reason to study the African tryanosome is that it causes a devastating disease in both humans and our livestock, the treatments for which are unsatisfactory, and whose elimination, or even eradication, we should all be striving for.